Pancreatic cancer is a disease that accounts for an estimated 43,000 cases and 36,000 deaths in the United States every year and is the 4th leading cause of cancer deaths among both men and women in the United States. Ductal adenocarcinomas are the most common form of pancreatic cancer, and about 80% of adenocarcinomas occur at the head of the pancreas, where they frequently cause obstructive jaundice (a blockage of the bile ducts). Pancreatic cancer can also cause severe upper abdominal pain; weight loss; splenic vein obstruction, resulting in splenomegaly, gastric and esophageal varices, and GI hemorrhage; and diabetes.
In over 90% of patients with pancreatic cancer, diagnosis does not occur until a late stage of cancer, because the disease is usually asymptomatic at early stages. Frequently, by the time patients present with symptoms of pancreatic cancer and are diagnosed with the disease, the cancer has spread to regional lymph nodes or metastasized to the liver or lung. Although the prognosis for patients diagnosed with pancreatic cancer varies with stage, the overall prognosis for the disease is poor, and less than 4% of all patients survive longer than 5 years, due in part to the fact that patients generally have an advanced stage of the disease at the time of diagnosis. About 80-90% of pancreatic cancers are surgically unresectable by the time of diagnosis because of metastasis or invasion of blood vessels. Therefore, the treatment options that are available for most pancreatic cancer patients are more limited than they would be if earlier detection of pancreatic cancer were available. Thus, detection of pancreatic cancer at an early stage would likely improve the mortality rates associated with this disease1-3.
Biomarkers are measurable biological and physiological parameters that can serve as indices for health-related assessments, such as diagnosis of disease. Nucleic acid and protein biomarkers are especially useful because they are amenable to bodily fluid tests (such as saliva tests), which are easier and more convenient to administer than tissue biopsy tests. With respect to detecting early stage pancreatic cancer, however, the current biomarkers and testing strategies that exist1,4-8 are limited in their usefulness because they are either confined to a small number of patients at greater risk, rely on invasive procedures, or lack the necessary sensitivity and specificity to be suitable for widespread screening9-11. For example, pancreas-associated antigen CA 19-9 is used to screen patients who are at high risk of developing pancreatic cancer, but it is not sensitive or specific enough to be suitable for general population screening. Additionally, the search for potential useful biomarkers of pancreatic cancer is further complicated by the existence of several benign pancreatic diseases, such as chronic pancreatitis, which has phenotypic overlap with early stage pancreatic cancer. In particular, the lack of specificity of currently used pancreatic cancer biomarkers is often due to the presence of these biomarkers in patients with chronic pancreatitis4,5.
Saliva has gained attention as a diagnostic fluid because it is simple to collect and readily accessible via a non-invasive procedure. Salivary constituents including DNA, RNA, protein, and bacteria have been studied as potential diagnostic markers for various diseases, such as oral disease15,16 17 18 and systemic disease19 20 21 22.
Given the importance of early detection for successful treatment of pancreatic cancer, and given the limitations of the currently existing strategies for detecting pancreatic cancer at an early stage, there is a need in the field for biomarkers of pancreatic cancer, and methods of using such biomarkers, that are minimally invasive and also sensitive and specific enough in detecting early-stage pancreatic cancer to be suitable for widespread screening of patients. The present invention addresses this need and others.